SGLT-2 inhibitors in diabetes: a focus on renoprotection

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

Influência do exercício físico crônico sobre a morfologia renal de ratos diabéticos experimentais

O diabetes mellitus é uma doença crônica caracterizada por alteraçöes bioquímicas relacionadas a deficiência de insulina. A atividade física realizada regularmente promove benéficas adaptaçöes estruturais e funcionais nos organismos diabéticos. O trabalho investigou possíveis alteraçöes glicêmicas e renais em ratos diabéticos sedentários e treinados. Os ratos foram distribuídos nos seguintes grupos: controle sedentário, controle treinado, diabético sedentário, diabético treinado. O programa de exerc1cio consistiu em nataçäo: 60 min/dia, 5 d/semana, 6 semanas. Ao final do período experimental os ratos foram sacrificados e retiradas amostras de sangue para análise de glicemia, insulina, albuminas e proteínas totais e retirados os rins para análises histológicas. Os cortes foram corados com (HE). A ANOVA mostrou elevaçäo na glicemia e reduçäo da insulina nos diabéticos. Näo foram encontradas diferenças significativas para proteínas totais e albumina. A análise histológica mostrou que os corpúsculos renais foram semelhantes entre os grupos CS e CT, mas apresentaram-se aumentados principalmente entre os DS. Portanto, o treinamento físico foi efetivo em reduzir os níveis glicêmicos, bem como, em melhorar os aspectos morfológicos renais dos diabéticos.(au)